Shensong Yangxin Capsule prevents diabetic myocardial fibrosis by inhibiting TGF-β1/Smad signaling

Abstract Ethnopharmacological relevance Shensong Yangxin Capsule (SSYX), a traditional Chinese herbal medicine, has long been used clinically to treat arrhythmias in China. However, the effect of SSYX on interstitial fibrosis in diabetic cardiomyopathy is unknown. The objective of this study was to investigate the effects of SSYX on myocardial fibrosis in diabetic rats. Materials and methods The antifibrotic effect of SSYX was investigated in streptozocin (STZ)-induced diabetic rats with high fat-diet (HFD). Fasting blood glucose, heart weight/body weight (HW/BW) ratio, total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) were measured. Echocardiography and histology examination were carried out to evaluate heart function. Expressions of Smad7, TGF-β1, collagen I (col-1), collagen III (col-3), MMP-2, MMP-9 and α-SMA mRNA in heart tissues were measured by real time polymerase chain reaction (PCR). TGF-β1, Smad2/3, p-Smad2/3 and Smad7 protein levels were measured by western blot analysis. Proliferation of cardiac fibroblast was detected via immunofluorescence. Results SSYX markedly decreased HW/BW ratio and improved the impaired cardiac function of type-2 diabetes mellitus (T2DM) rats. Transmission electron microscopy (TEM), haematoxylin and eosin (HE) and Masson staining results showed that SSYX attenuated cardiac fibrosis and collagen deposition in T2DM rats. Moreover, mRNA levels of TGF-β1, col-1, col-3, MMP-2, MMP-9 and α-SMA were downregulated, whereas Smad7 expression was upregulated after treatment with SSYX in rats with cardiac fibrosis. Furthermore, SSYX decreased protein levels of TGF-β1 and p-Smad2/3, and increased Smad7 expression. Conclusion TGF-β1/Smad signaling is involved in the cardiac fibrosis in diabetic cardiomyopathy and SSYX inhibits fibrosis and improves cardiac function via suppressing this pathway. Therefore, SSYX might be considered as an alternative therapeutic remedy for diabetic cardiomyopathy.